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Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez 2017 Wright State University

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Francisco J. Alvarez

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw ...


Tissue-Specific Mitochondrial Decoding Of Cytoplasmic Ca(2+) Signals Is Controlled By The Stoichiometry Of Micu1/2 And Mcu., Melanie Paillard, György Csordás, Gergö Szanda, Tünde Golenár, Valentina Debattisti, Adam Bartok, Nadan Wang, Cynthia Moffat, Erin L. Seifert, András Spät, György Hajnóczky 2017 Thomas Jefferson University

Tissue-Specific Mitochondrial Decoding Of Cytoplasmic Ca(2+) Signals Is Controlled By The Stoichiometry Of Micu1/2 And Mcu., Melanie Paillard, György Csordás, Gergö Szanda, Tünde Golenár, Valentina Debattisti, Adam Bartok, Nadan Wang, Cynthia Moffat, Erin L. Seifert, András Spät, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial Ca(2+) uptake through the Ca(2+) uniporter supports cell functions, including oxidative metabolism, while meeting tissue-specific calcium signaling patterns and energy needs. The molecular mechanisms underlying tissue-specific control of the uniporter are unknown. Here, we investigated a possible role for tissue-specific stoichiometry between the Ca(2+)-sensing regulators (MICUs) and pore unit (MCU) of the uniporter. Low MICU1:MCU protein ratio lowered the [Ca(2+)] threshold for Ca(2+) uptake and activation of oxidative metabolism but decreased the cooperativity of uniporter activation in heart and skeletal muscle compared to liver. In MICU1-overexpressing cells, MICU1 was pulled down by ...


The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan 2017 The University of Western Ontario

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration ...


Potent Single-Domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein In Its Prefusion State, Iebe Rossey, Morgan Gilman, Stephanie Kabeche, Koen Sedeyn, Daniel Wrapp 2017 Ghent University

Potent Single-Domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein In Its Prefusion State, Iebe Rossey, Morgan Gilman, Stephanie Kabeche, Koen Sedeyn, Daniel Wrapp

Open Dartmouth: Faculty Open Access Articles

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs ...


Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen MD, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress MD, Maria Tria Tirona MD 2017 Marshall University

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Mohamed Alsharedi

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC. Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided ...


Analysis Of Proprioceptive Sensory Innervation Of The Mouse Soleus: A Whole-Mount Muscle Approach, Martha Jean Sonner, Marie C. Walters, David R. Ladle 2017 Wright State University

Analysis Of Proprioceptive Sensory Innervation Of The Mouse Soleus: A Whole-Mount Muscle Approach, Martha Jean Sonner, Marie C. Walters, David R. Ladle

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle proprioceptive afferents provide feedback critical for successful execution of motor tasks via specialized mechanoreceptors housed within skeletal muscles: muscle spindles, supplied by group Ia and group II afferents, and Golgi tendon organs, supplied by group Ib afferents. The morphology of these proprioceptors and their associated afferents has been studied extensively in the cat soleus, and to a lesser degree, in the rat; however, quantitative analyses of proprioceptive innervation in the mouse soleus are comparatively limited. The present study employed genetically-encoded fluorescent reporting systems to label and analyze muscle spindles, Golgi tendon organs, and the proprioceptive sensory neuron subpopulations supplying ...


Targeting Hepatocellular Carcinoma Through Tgf-Β Pathway E3 Ligases, Kazufumi Ohshiro, Jian Chen, Shulin Li, Jon White, Asif Rashid, Lopa Mishra 2017 The George Washington University Medical School

Targeting Hepatocellular Carcinoma Through Tgf-Β Pathway E3 Ligases, Kazufumi Ohshiro, Jian Chen, Shulin Li, Jon White, Asif Rashid, Lopa Mishra

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.


The Role Of Uridine-Cytidine Kinase 2 In The Development Of Hepatocellular Carcinoma, Dehai Wu, Song Tao, Keunsoo Ahn, Nicha Wongjarupong, Lewis Roberts 2017 Virginia Commonwealth University

The Role Of Uridine-Cytidine Kinase 2 In The Development Of Hepatocellular Carcinoma, Dehai Wu, Song Tao, Keunsoo Ahn, Nicha Wongjarupong, Lewis Roberts

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.


Regulation Of Biliary Progenitor Cell Proliferation By Hedgehog Signaling In In Vivo And Ex Vivo Organoid Models, Nataliya Razumilava M.D., Junya Shiota M.D., Ramon Ocadiz-Ruiz Ph.D., Nureen Hanisah Mohamad Zaki, Kais Zakharia M.D., Michael Mathew Hayes, Juanita Lynn Merchant M.D., Ph.D. 2017 The University Of Michigan

Regulation Of Biliary Progenitor Cell Proliferation By Hedgehog Signaling In In Vivo And Ex Vivo Organoid Models, Nataliya Razumilava M.D., Junya Shiota M.D., Ramon Ocadiz-Ruiz Ph.D., Nureen Hanisah Mohamad Zaki, Kais Zakharia M.D., Michael Mathew Hayes, Juanita Lynn Merchant M.D., Ph.D.

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.


Mechanical Loading As Potential Treatment For Wnt Inhibitor Induced Bone Loss, Juraj Zahatnansky MD, Daniel Dick, Gabrielle Foxa, Robert Baker, Bart Williams PhD 2017 Western Michigan University Homer Stryker M.D. School of Medicine

Mechanical Loading As Potential Treatment For Wnt Inhibitor Induced Bone Loss, Juraj Zahatnansky Md, Daniel Dick, Gabrielle Foxa, Robert Baker, Bart Williams Phd

Research Day

The Wnt signaling pathway has been shown to play a role in bone homeostasis and carcinogenesis. On the one hand, a decrease in signaling has been associated with a decrease in bone mass, on the other, an increase in signaling with cancer development. LGK974 is a Wnt signaling inhibitor currently being investigated as a potential cancer therapeutic agent. This molecule inhibits Porcupine, a transmembrane protein necessary for Wnt ligand secretion. In light of the above and based on our preliminary data, treatment with LGK974 leads to bone mass loss. Our investigation aims to address whether such bone loss can be ...


An Rnai Screen To Identify Components Of A Polyamine Transport System, Adam J. Foley 2017 University of Central Florida

An Rnai Screen To Identify Components Of A Polyamine Transport System, Adam J. Foley

Honors Undergraduate Theses

Polyamines, specifically putrescine, spermidine, and spermine, are small cationic molecules found in all organisms. Cells can biosynthetically make these molecules, or alternatively, they can be transported from the extracellular environment. Malignant cells have been shown to require relatively high amounts of polyamines. There is a chemotherapeutic agent, DFMO, used to block the biosynthesis of polyamines. Many malignant cells can circumvent DFMO therapy by activating their transport system. A potential solution is to simultaneously block biosynthesis and transport of polyamines. However, little is known about the polyamine transport system in higher eukaryotes.

This thesis aims to add to the basic biological ...


Role Of Translation Initiation In Regulation Of Epithelial Junctions And Cell Motility, Fahda Fawaz Alsharief 2017 Virginia Commonwealth University

Role Of Translation Initiation In Regulation Of Epithelial Junctions And Cell Motility, Fahda Fawaz Alsharief

Theses and Dissertations

The integrity and barrier properties of intestinal epithelium are determined by specialized adhesive structures known as intercellular junctions; composed of adherens junctions (AJs), tight junctions (TJs) and focal adhesions that mediate cell-cell and cell matrix interactions, respectively. These two types of epithelial cell adhesions regulate each other during disruption and restitution of the epithelial barrier. Inflammatory cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are elevated during intestinal inflammation. The most notable effects of IFNγ and TNFα on intestinal epithelial homeostasis involve disruption of apical junctions and attenuation of cell migration. Although molecular mechanisms underlying these ...


Dynamics Of Mitotic Microtubules In Fission Yeast, Patrick Flynn 2017 University of Colorado, Boulder

Dynamics Of Mitotic Microtubules In Fission Yeast, Patrick Flynn

Undergraduate Honors Theses

Microtubules (MTs) are cytoskeletal polymers that assemble into a biomechanical complex known as the mitotic spindle. The spindle is responsible for the equal partitioning of chromosomes during cell division; an event known as mitosis. The dependence of proper chromosome segregation on the dynamics of individual microtubules (MTs) is not well understood or easy to study due to their small size and quick dynamics. Mathematical models and simulations have been constructed in order to better understand the physical basis of how the mitotic spindle accurately, or inaccurately, divides duplicated chromosomes during mitosis. These models rely on the dynamics parameters of individual ...


The Autophagy Initiator Ulk1 Sensitizes Ampk To Allosteric Drugs, Toby A. Dite, Naomi Ling, John W. Scott, Ashfaqul Hoque, Sandra Galic, Benjamin L. Parker, Kevin R.W. Ngoei, Christopher G. Langendorf, Matthew O'Brien, Mondira Kundu, Benoit Viollet, Gregory R. Steinberg, Kei Sakamoto, Bruce Kemp, Jonathan S. Oakhill 2017 Australian Catholic University

The Autophagy Initiator Ulk1 Sensitizes Ampk To Allosteric Drugs, Toby A. Dite, Naomi Ling, John W. Scott, Ashfaqul Hoque, Sandra Galic, Benjamin L. Parker, Kevin R.W. Ngoei, Christopher G. Langendorf, Matthew O'Brien, Mondira Kundu, Benoit Viollet, Gregory R. Steinberg, Kei Sakamoto, Bruce Kemp, Jonathan S. Oakhill

Faculty of Health Sciences Publications

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the β1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase in cells. Cellular β1-Ser108 phosphorylation by ULK1 was dependent on AMPK β-subunit myristoylation, metabolic stress associated with elevated AMP/ATP ratio, and the intrinsic energy sensing capacity of ...


Survival And Growth Of C57bl/6j Mice Lacking The Bk Channel, Kcnma1: Lower Adult Body Weight Occurs Together With Higher Body Fat, Susan T. Halm, Michael A. Bottomley, Mohammed M. Almutairi, Mauricio Di Fulvio, Dan R. Halm 2017 Wright State University - Main Campus

Survival And Growth Of C57bl/6j Mice Lacking The Bk Channel, Kcnma1: Lower Adult Body Weight Occurs Together With Higher Body Fat, Susan T. Halm, Michael A. Bottomley, Mohammed M. Almutairi, Mauricio Di Fulvio, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

Big conductance potassium (BK) channels contribute to K+ flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BKKO) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0– P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction. Births ...


Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty 2017 Marshall University

Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty

Theses, Dissertations and Capstones

The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h ...


Comparative Genetic Screens In Human Cells Reveal New Regulatory Mechanisms In Wnt Signaling, Andres M. Lebensohn, Ramin Dubey, Leif Neitzel, Ofelia Tacchelly-Benites 2016 Stanford University

Comparative Genetic Screens In Human Cells Reveal New Regulatory Mechanisms In Wnt Signaling, Andres M. Lebensohn, Ramin Dubey, Leif Neitzel, Ofelia Tacchelly-Benites

Open Dartmouth: Faculty Open Access Articles

The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the ...


The Origin Of Human White, Brown, And Brite/Beige Adipocytes, So Yun Min 2016 University of Massachusetts Medical School

The Origin Of Human White, Brown, And Brite/Beige Adipocytes, So Yun Min

GSBS Dissertations and Theses

During embryonic development, adipocytes emerge from microvasculature. Lineage-­‐tracing studies in mice have shown that adipocyte progenitors reside in the adipose tissue capillaries. However, the direct evidence of an association between adipocyte progenitors and vasculature in humans is lacking. A specific class of adipocytes (brown and beige/brite) expresses the uncoupling protein 1 (UCP1), which consumes glucose and fatty acids to generate heat. The abundance of UCP1- containing adipocytes correlates with a lean metabolically healthy phenotype in human. However, a causal relationship between the presence of these cells and metabolic benefits in human is not clear.

In this thesis, I ...


Calcium Uptake Hotspots In The Mitochondria Of Cardiac Muscle At The Interface With Dyadic Sr, Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Sheu, György Csordás 2016 Thomas Jefferson University

Calcium Uptake Hotspots In The Mitochondria Of Cardiac Muscle At The Interface With Dyadic Sr, Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction

• Control of the mitochondrial ATP production by SR-derived Ca2+ signals includes local, nanodomain Ca2+ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).

• Ca2+ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca2+-activated Ca2+ channel complex.

• The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).


An Examination Into The Relationship Between Iron Deficiency And Postpartum Depression, Sara A. Burroughs 2016 Liberty University

An Examination Into The Relationship Between Iron Deficiency And Postpartum Depression, Sara A. Burroughs

Senior Honors Theses

Postpartum depression is recognized as the most common complication of childbearing; however, its etiology remains fairly undetermined. Many different influences have been hypothesized as to what may cause postpartum depression, including changes in levels of various hormones (such as estrogen and progesterone), a decrease in serotonin, low levels of vitamin D, social factors, and iron deficiency. The lack of strong evidence for one specific cause makes it fairly clear that there are many factors that play a role in the development of postpartum depression. Iron deficiency is one issue that is thought to contribute to the development of postpartum depression ...


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